The invention relates to the field of medicine. In particular, it relates to recombinant cationic polypeptides and their use as biolubricant,
Biomacromolecules do not only fulfil complex functions inside the cell or within membranes, but proteinaceous materials may also play a very critical role at interfaces. One such example is biolubrication, where sliding surfaces coated with synthetic polymers and biological building blocks have been intensively investigated.[1] Biolubrication is an essential feature of health and can become impaired in the elderly or diseased.[2] Sjögren's syndrome, for instance, is a disease causing a variety of symptoms like dry eyes,[3] dry mouth,[4] vaginal dryness[5] and excessive friction and wear at the knee and hip joints.[6]
Biolubrication is mediated by glandular secretions containing (glyco-) proteins that adsorb at the sliding interface and form a conditioning film. Although water forms the basis of all biolubrication phenomena, it is easily removed from in between sliding surfaces during physiological activities associated with high contact pressures. To counter this, conditioning films providing biolubrication contain different glycoproteins that retain water molecules to generate repulsive hydration forces at the interface of the sliding surfaces.[7,8] Oral lubrication by adsorbed salivary conditioning films (SCFs)[9] is essential to facilitate speaking and mastication and protects against wear due to erosion[10] and abrasion.[11]
Maintenance of adequate biolubrication in the oral cavity is not only challenged by disease and aging, but also by high contact pressures. Contact pressures on molar surfaces during mastication can be as high as 86 MPa[12] which is one order of magnitude higher than the pressures experienced in hip and knee joints.[13] This load makes the maintenance and restoration of lubrication more challenging in the oral cavity than in other parts of the human body where articulating surfaces are involved.
Disorders associated with reduced or impaired biolubrication include xerostomia. Xerostomia refers to dry mouth caused by a lack of saliva and is often associated with some form of salivary gland dysfunction. In the field of oral care, xerostomia is problematic as saliva provides a protective effect on the teeth and can dilute or wash away harmful bacteria and/or food particles from the oral cavity. Failure to protect the teeth or allowing an accumulation of harmful bacteria/food particles can lead to bad breath (halitosis) or more seriously, to infections of the mucosal or periodontal tissue of the oral cavity.
Often, oral dryness is due to insufficient retention of water molecules in adsorbed SCFs due to low salivary flow rates (<1 mL min−1) or dysfunction of a particular salivary gland.[2] Patients suffering from oral dryness symptoms are treated with artificial salivas, often containing lubricants like pig gastric mucins, polyacrylic acid and carboxymethyl cellulose.[14,15] However, artificial salivas only yield temporary relief in patients, as the adsorbed conditioning films are unable to sufficiently retain water due to lack of structural integrity.
Another disease associated with impaired biolubrication is dry eye syndrome or xerophthalmia. Xerophthalmia is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tears film instability with potential damage to the ocular surface. Multiple causes can lead to xerophthalmia, which is more common in elderly people. Amongst diseases causing xerophthalmia are found: vitamin A deficit, Sjögren syndrome, rheumatoid arthritis and other rheumatologic diseases, chemical or thermal burns, drugs such as atenolol, chlorpheniramine, hydrochlorothiazide, isotretinoin, ketorolac, ketotifen, levocabastin, levofloxacin, oxybutynin, tolterodine.
Recognizing the need for an improved approach to restore or enhance biolubrication, e.g. in the treatment of xerostomia or xerophthalmia, the present inventors set out to develop new biolubricants. In particular, they aimed at providing a biolubricant system that does not involve the administration of heterologous or artificial material e.g. in a bodily cavity, but which relies on strengthening the existing, though often impaired, endogenous conditioning film.